A wide range of clinical and pathophysiologic studies were performed in a large number of patients with the idiopathic hypereosinophilic syndrome (HES). Mechanisms of organ system damage and dysfunction were delineated predominantly regarding the endocardiomyopathy of the HES. In vitro stem cell studies delineated the heterogeneous levels of abnormalities in patients with HES. Aggressive medical and surgical approach to the heart disease as well as chemotherapeutic regimens has led to dramatic improvement in prognosis in HES. Various abnormalities at the B and/or T cell levels were precisely delineated in patients with Sjogren's syndrome, SLE, Hashimoto's thyroiditis. An isolated defect in NK cells was described in patients with the Chediak-Higashi syndrome constituting the first description of a primary human immunodeficiency disease with an isolated defect in NK cells. The effect of cyclophosphamide on NK function in patients was studied and demonstrated a marked suppression of function, potentially explaining the occurrence of lymphoproliferative diseases in patients receiving cytotoxic agents. Normal individuals with the HLA-B8, DRw3 haplotype were shown to have abnormalities of RES function as well as defects in subsets of T cells and spontaneous secretion of Ig by B cells.